Plasma lipoproteins play important roles in the release of lipids from liver, in the transport of lipids through plasma, and in the absorption of lipid from the gastrointestinal tract. The concentrations of lipoproteins in plasma depend upon their rates of secretion into plasma (input) relative to rates of catabolism (output). Both input and output rates may be regulated by genetically determined metabolic controls. Input is affected by factors such as diet, hormones, and the metabolic state of the animal and may be limited by the availability of the apolipoproteins. Output depends upon at least two enzymes and a number of "cofactor" peptides which form parts of the lipoproteins themselves, i.e., the apolipoproteins. Thus, the peptide moieties of lipoproteins are important in the synthesis, structure and catabolism of lipoproteins. The objective of this research is to study the rates of secretion of the apolipoproteins and the composition of lipoproteins under basal conditions and to ascertain how altered rates of secretion produced by a number of metabolic perturbations affect lipoprotein compositions. The isolated perfused rat liver, a model system particularly suitable for these studies, will be used in conjunction with radioimmunoassays for rat LDL and HDL-proteins and other procedures for the quantification of lipoprotein lipids, peptides, and peptide synthetic rates. It is hoped that the information gained from this model system will lead to the design of more effective measures for the control of lipoprotein metabolism in man, resulting in the amelioration of the problem of atherosclerosis and other diseases related to abnormalities of lipoprotein metabolism.